Antineoplastic Agents ANTIBETABOLITES

Drug Mechanism Clinical Use Toxicity Methotrexate (MTX) Folic acid analog that inhibits

dihydrofolate reductase to decrease dTMP and decrease DNA and Protein synthesis

Leukemia, lymphoma,

choriocarcinoma

l. Myelosuppression, which is reversible

with leucovorin

(folinic acid) "rescue."

2. Macrovesicular fatty change in liver.

3. Mucositis. 4. Teratogenic.

5-fluorouracil (5-FU) Pyrimidine analog bioactivated to 5F-

dUMP, which covalently complexes

folic acid.

Colon cancer and other solid tumors,

basal cell carcinoma, synery with

MTX

l. Myelosuppression, which is not reversible

with leucovorin.

Overdose: "rescue"

with thymidine.

2. Photosensitivity

6-mercaptopurine (6-MP) Purine analog to decrease purine

synthesis

Leukemias, lymphomas (not CLL or

Hodgkins)

Bone marrow, GI,

liver. Metabolized

by xanthine oxidase;

thus I toxicity with allopurinol.

6-thioguanine (6-TG) Same as 6-MP Acute Lymphoid leukemia Bone marrow depression, liver.

Can be given with

allopurinol.

Cytarabine (ara-C) Pyrimidine antagonist to decrease

DNA polymerase

AML, ALL, high grade non hodgkins

lymphoma

Leukopenia,

thrombocytopenia,

megaloblastic anemia.

ANTIBIOTICS

Drug Mechanism Clinical Use Toxicity

Dactinomycin (Actinomycin D) Intercalates in DNA Wilms tumor, Ewings sarcoma, rhabdomyosarcoma

Myelosuppression.

Doxorubicin (Adriamycin); daunorubicin

Generate free radicals. Noncvalently intercalate in DNA to breaks in DNA to decrease replication

Hodgkins lymphomas; also for myelomas, sarcomas, and solid tumors

Cardiotoxicity,

myelosuppression, and

alopecia. Toxic to tissues

with extravasation. Bleomycin Induces free radical formation, which

causes breaks in DNA strands Testicular cancer, Hodgins lymphoma Pulmonary fibrosis, skin

changes. Minimal

myelosuppression. Etoposide (VP-16); teniposide Inhibits topoisomerase II increase

DNA degradation Small cell carcinoma of the lung and prostate, testicular carcinoma

Myelosuppression, Gl

irritation, alopecia.

ALKYLATING AGENTS

Drug Mechanism Clinical Use Toxicity

Cyclophosphamide; ifosfamide Covalently X link DNA at guanine N-7. Require bioactivation by liver

Non hodgkins lymphoma, breast and ovarian carcinomas. Also immunosuppressant

Myelosuppression;

hemorrhagic cystitis,

partially prevented

with mesna (thiol

group of mesna binds

toxic metabolite). Nitrosureas (carmustine, lomustine, semustine, streptozocin)

Require bioactivation. Cross blood brain barrier to CNS

Brain tumors (including glioblastoma multiforme)

CNS toxicity (dizziness,

ataxia).

Busulfan Alkylates DNA CML. Also used to ablate patients bone marrow before bone marrow transplantation

Pulmonary fibrosis,

hyperpigmentation.

MICROTUBULE INHIBITORS

Drug Mechanism Clinical Use Toxicity

Vincristine; vinblastine Alkaloids that bind to tubulin in M-phase and block polymerization of microtubules so that mitotic spindle cannot form. Microtubules are the vines of your cells.

Hodgkins lymphoma, Wilms tumor choriocarcinoma

Vincristine- neurotoxicity (areflexia, peripheral block polymerization choriocarcinoma. neuritis), paralytic ileus. VinBLASTine BLASTs Bone marrow

Paclitaxel Hyperstabilize polymerized microtubules in M-phase so that mitotic spindle cannot break down. It is Taxing to stay polymerized.

Ovarian and breast carcinomas Myelosuppression and hypersensitivity.